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Yorodumi- PDB-5i0l: Crystal structure of the catalytic domain of MMP-12 in complex wi... -
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-Basic information
Entry | Database: PDB / ID: 5i0l | ||||||
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Title | Crystal structure of the catalytic domain of MMP-12 in complex with a selective sugar-conjugated arylsulfonamide carboxylate water-soluble inhibitor (DC27). | ||||||
Components | Macrophage metalloelastase | ||||||
Keywords | HYDROLASE / Inhibitor / complex / glycoconjugate / metalloprotease | ||||||
Function / homology | Function and homology information macrophage elastase / negative regulation of endothelial cell-matrix adhesion via fibronectin / bronchiole development / positive regulation of epithelial cell proliferation involved in wound healing / elastin catabolic process / regulation of defense response to virus by host / positive regulation of type I interferon-mediated signaling pathway / wound healing, spreading of epidermal cells / negative regulation of type I interferon-mediated signaling pathway / lung alveolus development ...macrophage elastase / negative regulation of endothelial cell-matrix adhesion via fibronectin / bronchiole development / positive regulation of epithelial cell proliferation involved in wound healing / elastin catabolic process / regulation of defense response to virus by host / positive regulation of type I interferon-mediated signaling pathway / wound healing, spreading of epidermal cells / negative regulation of type I interferon-mediated signaling pathway / lung alveolus development / response to amyloid-beta / Collagen degradation / collagen catabolic process / extracellular matrix disassembly / positive regulation of interferon-alpha production / core promoter sequence-specific DNA binding / collagen binding / Degradation of the extracellular matrix / extracellular matrix organization / extracellular matrix / cellular response to virus / metalloendopeptidase activity / protein import into nucleus / endopeptidase activity / sequence-specific DNA binding / serine-type endopeptidase activity / calcium ion binding / negative regulation of transcription by RNA polymerase II / positive regulation of transcription by RNA polymerase II / proteolysis / extracellular space / zinc ion binding / extracellular region / nucleus / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.45 Å | ||||||
Authors | Stura, E.A. / Rosalia, L. / Cuffaro, D. / Tepshi, L. / Ciccone, L. / Rossello, A. | ||||||
Citation | Journal: Chemmedchem / Year: 2016 Title: Sugar-Based Arylsulfonamide Carboxylates as Selective and Water-Soluble Matrix Metalloproteinase-12 Inhibitors. Authors: Nuti, E. / Cuffaro, D. / D'Andrea, F. / Rosalia, L. / Tepshi, L. / Fabbi, M. / Carbotti, G. / Ferrini, S. / Santamaria, S. / Camodeca, C. / Ciccone, L. / Orlandini, E. / Nencetti, S. / ...Authors: Nuti, E. / Cuffaro, D. / D'Andrea, F. / Rosalia, L. / Tepshi, L. / Fabbi, M. / Carbotti, G. / Ferrini, S. / Santamaria, S. / Camodeca, C. / Ciccone, L. / Orlandini, E. / Nencetti, S. / Stura, E.A. / Dive, V. / Rossello, A. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5i0l.cif.gz | 160.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5i0l.ent.gz | 126.6 KB | Display | PDB format |
PDBx/mmJSON format | 5i0l.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5i0l_validation.pdf.gz | 1 MB | Display | wwPDB validaton report |
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Full document | 5i0l_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 5i0l_validation.xml.gz | 20.7 KB | Display | |
Data in CIF | 5i0l_validation.cif.gz | 28.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/i0/5i0l ftp://data.pdbj.org/pub/pdb/validation_reports/i0/5i0l | HTTPS FTP |
-Related structure data
Related structure data | 5i12C 5i2zC 5i3mC 5i43C 5i4oC 4h84S S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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2 |
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Unit cell |
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-Components
-Protein , 1 types, 2 molecules AB
#1: Protein | Mass: 17615.670 Da / Num. of mol.: 2 / Fragment: UNP residues 106-263 / Mutation: F171D Source method: isolated from a genetically manipulated source Details: catalytic domain of MMP-12 with F171D mutation. / Source: (gene. exp.) Homo sapiens (human) / Tissue: macrophage / Gene: MMP12, HME / Details (production host): propagated in E.C. XL1-Blue / Production host: Escherichia coli BL21(DE3) (bacteria) / Variant (production host): star / References: UniProt: P39900, macrophage elastase |
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-Non-polymers , 8 types, 321 molecules
#2: Chemical | Mass: 762.847 Da / Num. of mol.: 2 / Mutation: F171D Source method: isolated from a genetically manipulated source Formula: C34H42N4O12S2 / Details: catalytic domain of MMP-12 with F171D mutation. / Source: (gene. exp.) Homo sapiens (human) / Tissue: macrophage / Details (production host): propagated in E.C. XL1-Blue / Production host: Escherichia coli BL21(DE3) (bacteria) / Variant (production host): star / References: macrophage elastase #3: Chemical | ChemComp-ZN / #4: Chemical | ChemComp-CA / #5: Chemical | ChemComp-PGO / | #6: Chemical | #7: Chemical | ChemComp-PEG / | #8: Chemical | ChemComp-DMS / | #9: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.15 Å3/Da / Density % sol: 42.82 % / Description: thin plates |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 8.5 Details: Protein-inhibitor complex: hMMP12 0.631 milli-M + 0.010 M Acetohydroxamic acid + 0.005 M inhibitor DC27, 10% DMSO. precipitant: 34% PEG 4K, 1.5 M imidazole piperidine, pH 8.5, Dioxane 25% ...Details: Protein-inhibitor complex: hMMP12 0.631 milli-M + 0.010 M Acetohydroxamic acid + 0.005 M inhibitor DC27, 10% DMSO. precipitant: 34% PEG 4K, 1.5 M imidazole piperidine, pH 8.5, Dioxane 25% Cryoprotectant: 40% Cryomix: (12.5 % diethylene glycol + 12.5 % glycerol + 12.5 % 1,2-propanediol + 12.5 % 2,3-butanediol + 25 % DMSO + 30 % 1,4-dioxane), 25% MPEG 6K, 0.1 M AAB (Na acetate, ADA, Bicine: 10% acid/90% basic), pH 8.5 Temp details: cooled incubator |
-Data collection
Diffraction | Mean temperature: 100 K / Ambient temp details: cryonozzle |
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Diffraction source | Source: SYNCHROTRON / Site: ESRF / Beamline: MASSIF-1 / Wavelength: 0.965 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jan 29, 2015 / Details: Mirrors |
Radiation | Monochromator: Single Silicon (111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.965 Å / Relative weight: 1 |
Reflection | Resolution: 2.45→45 Å / Num. obs: 11195 / % possible obs: 99.2 % / Observed criterion σ(I): -3 / Redundancy: 3.14 % / Biso Wilson estimate: 28.91 Å2 / Rmerge(I) obs: 0.111 / Rsym value: 0.093 / Net I/σ(I): 9.6 |
Reflection shell | Resolution: 2.45→2.51 Å / Redundancy: 3.23 % / Rmerge(I) obs: 0.23 / Mean I/σ(I) obs: 5.23 / % possible all: 99.3 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4H84 Resolution: 2.45→44.22 Å / SU ML: 0.38 / Cross valid method: THROUGHOUT / σ(F): 1.05 / Phase error: 29.36
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | ||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.45→44.22 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Origin x: 10.3639 Å / Origin y: 15.2171 Å / Origin z: 14.5706 Å
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Refinement TLS group | Selection details: ALL |